Microfluidic Systems to Mimic the Blood-Brain Barrier: from Market to Engineering Challenges and Perspectives.

Studying and understanding complex biological systems is a challenge that requires technologies that go beyond traditional cell culture methods. Among the new technologies that have been developed in recent times, blood-brain barrier-on-a-chip (BBB-on-a-chip) models are becoming popular. Due to their ability to integrate fluid flow, which is absent in traditional static models, it has been possible to create a cellular microenvironment that mimics blood vessels and blood flow. In addition, the possibility of coculturing different cell types in multicellular models allows the observation of their interactions and increases interest in these systems. With different possibilities in terms of prototyping techniques (e.g., laminate manufacturing, molding, and 3D impression), chip designs (e.g., planar and cylindrical configurations), and materials (e.g., thermoplastics, elastomers, and hydrogels), the number of publications in the BBB research field has significantly increased in the last five years. In parallel, the emergence and consolidation of several companies have made the commercialization and application of these chips possible, mainly in the pharmaceutical area, which is not yet integrated into the drug development pipeline. In this context, the present review describes the intersection between technique, market, and applications that mimic the BBB. We showed organ-on-a-chip (OoC) market growth and the collaborative research between the main OoC supplier companies and industrial collaborators. Also, we present an overview of the primary fabrication methods used in constructing the OoC systems and their application in developing the BBB models. In addition, we discussed the BBB-on-a-chip designs developed in the last five years, including their engineering aspects (such as materials, dimensions, and configuration), characterization, and challenges in mimicking the BBB.